Melanocyte-stimulating hormone receptor

UniProt Q01726 Organism Homo sapiens Gene MC1R, MSHR

Also known as: MC1R, MSHR

Function

G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein. Upon activation, MC1R couples with the G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway. This activation promotes melanogenesis, resulting in the production of eumelanin (black/brown) and pheomelanin (red/yellow) in melanocytes. MC1R interacts with G protein-coupled receptor opsin 3/OPN3, which couples to G(i) proteins and inhibits the alpha-MSH-induced cAMP response, thereby reducing melanin synthesis. Binding to Agouti/ASP precludes alpha-MSH-induced signaling, thereby downregulating melanogenesis (By similarity). Additionally, interaction with MGRN1 displaces the G(s) protein, further suppressing MC1R signaling.

Classification

Family (Pfam): PF00001 7tm_1
InterPro: GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Melcrt_ACTH_rcpt, MSH_rcpt
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 5

7F4D EM 3.00A
7F4F EM 2.90A
7F4H EM 2.70A
7F4I EM 3.10A
9K3P EM 2.98A

A predicted model is available from AlphaFold.

Gene Ontology · 22

Disease associations

obsolete skin/hair/eye pigmentation, variation in, 2 MONDO:0044259
OMIM:613098 RAW:OMIM_613098
melanoma, cutaneous malignant, susceptibility to, 5 MONDO:0013133

Drugs targeting this protein · 3

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Pro-opiomelanocortin 2 shared papers
Opsin-3 1 shared papers
Adrenocorticotropic hormone receptor 2 shared papers
E3 ubiquitin-protein ligase MGRN1 1 shared papers
Melanocyte-stimulating hormone receptor 1 shared papers
Melanocyte-stimulating hormone receptor 1 shared papers
Protein FAM185A 1 shared papers
Melanocortin receptor 3 1 shared papers
Melanocortin receptor 4 1 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 1 shared papers
Proteasome assembly chaperone 4 1 shared papers
Kit ligand 1 shared papers

Literature · 29 cited papers

Structural mechanism of calcium-mediated hormone recognition and Gbeta interaction by the human melanocortin-1 receptor. Cell Res. · 2021
Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor. Proc. Natl. Acad. Sci. U.S.A. · 2019
Genetic modifiers of multiple sclerosis progression, severity and onset. Clin. Immunol. · 2017
Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas. J. Biol. Chem. · 2009
Identification and functional analysis of novel variants of the human melanocortin 1 receptor found in melanoma patients. Hum. Mutat. · 2009
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature · 2008
Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat. Genet. · 2007
MC1R: three novel variants identified in a malignant melanoma association study in the Spanish population. Carcinogenesis · 2007
Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians. Hum. Genet. · 2006
Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum. Mol. Genet. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc. Natl. Acad. Sci. U.S.A. · 2003
… and 17 more in the literature graph

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